Nebulette

Nebulette is a cardiac-specific isoform belonging to the nebulin family of proteins. It is encoded by the NEBL gene. This family is composed of 5 members: nebulette, nebulin, N-RAP, LASP-1 and LASP-2. Nebulette localizes to Z-discs of cardiac muscle and appears to regulate the length of actin thin filaments.

NEBL
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4F14
Identifiers
Aliases	NEBL, nebulette, LASP2, LNEBL
External IDs	OMIM: 605491; MGI: 1921353; HomoloGene: 31379; GeneCards: NEBL; OMA:NEBL - orthologs
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10p12.31 Start 20,779,973 bp[1] End 21,174,187 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 A3 Start 17,343,909 bp[2] End 17,731,464 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right ventricle myocardium myocardium of left ventricle optic nerve cardiac muscle tissue of right atrium apex of heart glomerulus metanephric glomerulus right auricle of heart Brodmann area 23 Top expressed in interventricular septum atrium myocardium of ventricle atrioventricular valve vestibular sensory epithelium ciliary body right lung lobe left lung lobe mammillary body deep cerebellar nuclei More reference expression data BioGPS n/a
Gene ontology Molecular function filamin binding cytoskeletal protein binding actin filament binding actin binding structural constituent of muscle tropomyosin binding protein binding Cellular component cytoplasm Z discdkac extracellular exosome I band stress fiber Biological process cardiac muscle thin filament assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10529 74103 Ensembl ENSG00000078114 ENSMUSG00000053702 UniProt O76041 Q5JUU7 Q9DC07 Q0II04 RefSeq (mRNA) NM_001173484 NM_006393 NM_016365 NM_213569 NM_028757 NM_001362722 RefSeq (protein) NP_001166955 NP_006384 NP_998734 NP_001364251 NP_001364252 NP_001364253 NP_001364254 NP_001364255 NP_001364256 NP_001364257 NP_083033.1 NP_083033 NP_001349651 Location (UCSC) Chr 10: 20.78 – 21.17 Mb Chr 2: 17.34 – 17.73 Mb PubMed search [3] [4]
Wikidata
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Structure

Nebulette is a 116.4 kDa protein composed of 1014 amino acids.^[5][6] As a member of the nebulin family of proteins, nebulette is characterized by 35 amino acid stretches of ‘‘nebulin repeats’’, which are actin binding domains containing a conserved SDxxYK motif.^[7] Like nebulin, nebulette has an acidic region with unknown structure at its N-terminus, and a serine-rich region adjacent to an SH3 domain at its C-terminus.^[8] Though nebulette shares structural features with nebulin, nebulin is expressed preferentially in skeletal muscle and has an enormous size (600-900 kDa), while nebulette is expressed in cardiac muscle at Z-disc regions and is significantly smaller (roughly 1/6 of the size).^[9] Nebulette interacts with actin, tropomyosin, alpha-actinin.^[10] Xin, and XIRP2.^[11]

Function

Nebulette was identified in 1995 by Moncman and Wang using primary cultures of chicken embryonic cardiomyocytes by immunoprecipitations with certain anti-nebulin monoclonal antibodies.^[12] Normal expression of nebulette is essential for the assembly and contractile function of myofibrils.^[13] Specifically, nebulette appears to regulate the stability and length of actin thin filaments, as well as beating frequencies of cardiomyocytes; reduction of full-length nebulette protein in cardiomyocytes resulted in reduced thin filament lengths, depressed beating frequencies and loss of thin filament regulatory proteins troponin I and tropomyosin.^[14][15]

Clinical significance

Mutations in the NEBL gene have been associated with dilated cardiomyopathy.^[16] Studies in transgenic mice have supported their causative role in endocardial fibroelastosis and dilated cardiomyopathy.^[17]